OPTIC ATROPHY IN WOLFRAM (DIDMOAD) SYNDROME

Wolfram syndrome is the association of diabetes mellitus and optic atr ophy, also called DIDMOAD (diabetes insipidus, diabetes mellitus, opti c atrophy and deafness), Incomplete characterisation has caused diagno stic confusion; we therefore undertook a nationwide cross-sectional ca se finding study, We identified 45 patients with Wolfram syndrome, med ian age 29 years, All patients fulfilled the ascertainment criteria (j uvenile onset diabetes mellitus and optic atrophy), Optic atrophy pres ented in 38 patients with reduced visual acuity and colour vision defe ct (median age 11 years), progressing to visual acuity of 6/60 or less in 35 patients (median time 8 years, range 1-25 years), Visual field examinations recorded before acuity deteriorated showed central scotom as with peripheral constriction, Blind patients had absent pupillary r eflexes, Horizontal nystagmus was seen in patients with other signs of cerebellar degeneration, There was no pigmentary retinal dystrophy; o nly 3 patients had background diabetic retinopathy, despite a median d uration of diabetes of 24 years, Electroretinography was normal in 3 p atients and showed reduced amplitude in 3 patients; visual evoked resp onses were abnormal (10/10 patients: reduced amplitude to both hash an d pattern stimulation), Magnetic resonance imaging showed generalised brain atrophy with reduced signal from the optic nerves and chiasm, A postmortem brain specimen from one patient revealed atrophy of the opt ic nerves, chiasm, cerebellum and brainstem, We found no evidence of m itochondrial genome defects or rearrangements, This primary neurogener ative disorder presents with diabetes mellitus and progressive optic a trophy, probably due to pathology in the optic nerve.